Docosahexaenoic Acid Increases the Brain Resolution Lipid Mediators of Inflammation in Rat Pups Prenatally Exposed to Alcohol

The fetal alcohol spectrum disorder (FASD/FAS) is a chronic inflammatory process of the fetal brain induced by alcohol and mediated by pro-inflammation (PILM) and pro-resolution (PRLM) lipid mediators of inflammation. DHA (Docosahexaenoic acid) is an essential precursor of PRLM. A study of the response by the lipid mediators of inflammation to alcohol insult and DHA supplementation can provide vital information on the pathogenesis of FASD/FAS and the potential ameliorative role of DHA. Four groups of timed pregnant rats were studied: Control, low dose (1.6 g/kg/day) and high dose (2.4 g/kg/day) alcohol and high dose alcohol (2.4 g/kg/day) + DHA, (1250 mg/kg/day of DHA). The pups were delivered on day 20, and their whole brain was examined for lipid mediators by liquid chromatography mass spectroscopy. The following biomarkers of brain lipid mediators were studied, viz., PILM (LTB4, PGE2, PGF2a, TXB2) and PRLM (LXA5, 4-HDoHE,17-HDoHE and MaR1n-3, DPA). The brain PILM and PRLM concentrations decreased sig-nificantly (p< 0.001) with high dose alcohol. However, high dose alcohol + DHA resulted in a significant (p< 0.001) increase in PRLM levels, viz, LXA5, MaR1n-3 DPA, 17-HDoHE and threefold increase in 4-HDoHE. We conclude that brain lipid inflammation can be ameliorated by DHA by mobilizing PRLM.